The present invention relates to a process for preparing optically active 2-halo-1-phenyl ethanol having the general formula [I*]: ##STR4## wherein X is a halogen atom, by asymmetrically reducing 2-halo-acetophenone having the general formula [III]: ##STR5## wherein X is as above, to give optically active 2-halo-1-phenyl ethanol, (R)-form or (S)-form, employing the microorganism. ##STR6##
Since optically active 2-halo-1-phenyl ethanol has two highly reactive functional groups and can also be easily converted into optically active styrene oxide which has a high reactivity, it is a very useful starting material for synthesizing various drugs, veterinary drugs, agricultural chemicals, perfumes and the like.
Hitherto, several methods have been reported for preparing optically active 2-halo-1-phenyl ethanol by employing the enzyme or the microorganism. One of these methods is to asymmetrically reduce 2-chloro-acetophenone by employing Saccharomyces cerevisiae to give (R)-2-chloro-1-phenyl ethanol (D. D. Ridley et al., J. Chem. Soc. Chem. Comm., 400 (1975)). The other method is to asymmetrically reduce 2-chloro-acetophenone or 2-bromoacetophenone by employing Cryptococcus macerans to give (R)-2-chloro-1-phenyl ethanol or (R)-2-bromo-1-phenyl ethanol (M. Imuta et al., J. Org. Chem., 45, 3352 (1980)). However, these methods using the above microorganisms give (R)-2-chloro-1-phenyl ethanol with low optical activities, i.e. about 85% enantiomer excess (e.e.), as calculated by the present inventors, and with low productivities. Therefore, it is obvious that these methods are not suited for the industrial production. Further, these methods product only (R)-form but not (S)-form.
Another method is to subject an ester of (+)-2-halo-1-phenyl ethanol with fatty acid to the action of Rhizopus nigricans to give (R)-2-halo-1-phenyl ethanol (M. Imuta et al., Tetrahedron Lett., 22, 2527 (1981)). Also according to this method, only very low optical purity is obtained.
By the result of the continuous effort of the present inventors in order to establish a process for preparing both enantiomers of 2-halo-1-phenyl ethanol with a good optical purity and yield by asymmetrically reducing 2-halo-acetophenone by employing the various microorganisms, the inventors have found the microorganisms capable of converting 2-halo-acetophenone into (S)-2-halo-1-phenyl ethanol and the microorganisms which can convert 2-halo-acetophenone into (R)-2-halo-1-phenyl ethanol with an excellent optical purity.